ETec_Lecture3: Tissue organization and function
(epithelial, connective, muscular and nervous).
Tissue Biology
A tissue is a collection of cells and ECM that perform a given function.
There are 4 main types of tissues:
   •   Epithelial Tissue
          o Lining, Transport, Secretion and Absorption
   •   Connective Tissue
          o Support, Strength, Elasticity
   •   Muscle Tissue
          o Movement
   •   Nervous Tissue
          o Information Synthesis, Communication and Control
There are between 400-1000 cell types. These Cell types are grouped in 7 classes in mature human
body:
   1. Blood
   2. Myocyte (muscle fibers)
   3. Epithelial & Endothelial (endothelial is a epithelial layer that covers heart and blood vessels)
             o Epithelial cells:
                     ▪ Grow in contiguous 2D sheets
                     ▪ They have polarity
                     ▪ Connected with their neighbours and bound to basal lamina (cannot migrate)
             o Mesenchymal Cells:
                     ▪ They can migrate
                     ▪ Their growth is contact-inhibited
                     ▪ Can differentiate into osteoblasts, chondrocytes, fibroblasts
   4. Stem, germ & pericyte
   5. Adipocyte
   6. Neuron & Glial
   7. Fibroblast & Osteoid
Depending on the tissue they can have ½ different types of cells.
Talking about Tissues
Epithelial Tissue
   •   Are composed of closely aggregated polyhedral cells with little EC substance but showing strong
       adherence to each other (tight junctions, desmosomes, adherens junctions, gap junctions)
   •   Epithelial Tissue: THE PINK ONE!
   •   Are not irrigated by blood vessels
   •   Are not inervated
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   •   Main Functions:
          o Covering and lining of surfaces
          o Absorption (intestines)
          o Secretion (glands)
          o Sensation (olfactory neuroepithelium)
   •   Epithelial classification is based on:
          o Number of cell layers:
                   ▪ Simple (1 layer)
                   ▪ Stratified (multiple layers)
          o Cell Shape
                   ▪ Squamous (‘pavimentoso’)
                   ▪ Cuboid
                   ▪ Columnar
                   ▪ Pseudostratified (has 1 layer but looks like more – because the nuclei seems to be
                      in different levels)
          o Presence of cell specializations
                   ▪ Microvilli: increase the cell surface area
                   ▪ Cilia: allows a current of fluid to be propelled in one direction
Types of epithelial tissues
   ❖ Endothelium: lines blood and lymph vessels
   ❖ Mesothelium: lines certain body cavities (pericardium, pleura, peritoneum)
Connective Tissue
   •   Are composed mainly of ECM (unlike other tissues).
   •   The wide variety reflects variations in the composition and amount of cells and ECM.
   •   Originated from the mesenchyme (an embryonic tissue) that develops from mesoderm.
   •   Main Functions:
          o Provide and maintain form in body
          o Structural
          o Metabolic aid for other tissues (specifically epithelial tissue)
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•   Cell Types in connective Tissue: (principal groups in yellow)
       o They are derived by:
               ▪ Mesenchymal cells: Fibroblasts, adipocytes, osteoblasts
               ▪ Hematopoietic cells: the other ones
          ❖ Fibroblasts
                o Synthesize and secrete ECM proteins, GAGs and proteoglycans and also GF
                o In adults, they rarely divide unless additional fibroblasts are needed
                o Fibroblasts that are actively engaged in synthesis are richer in mitochondria,
                   Golgi complex, and rough ER than are quiescent fibroblasts (fibrocytes)
                o Fibroblasts can produce signaling molecules.
          ❖ Macrophages and mononuclear phagocyte system
                o Macrophages are polymorphic phagocytic cells.
                o Very rich in lysosomes
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❖ Plasma cells (Plasmocytes)
     o Are derived from B lymphocytes and produces antibodies.
     o The cell contains a well-developed rough ER, with dilated cisternae containing
        immunoglobulins (antibodies).
     o In plasma cells, the secreted proteins do not aggregate into secretory
        granules.
     o Very rich in endoplasmic reticulum and ribosomes
❖ Adipose Tissue
     o Rich in adipocytes which are also found isolated or in small groups in other to
        connective tissues is highly vascularized.
     o Largest organ in the body
            ▪ Yellow/White (unilocular)
                    • Stores energy as triglycerides
            ▪ Brown (multilocular)
                    • Produces heat and is abundant in newborns (and hibernating
                        animals)
     o How do we store lipids? WHITE
            ▪ Triglycerides are transported in blood from the intestine and liver by
                lipoproteins known as chylomicrons and VLDLs.
            ▪ In adipose tissue capillaries, these lipoproteins are partly broken down
                by lipoprotein lipase, releasing fatty acids
            ▪ The free fatty acids diffuse from the capillary into the adipocyte, where
                they are re-esterified to glycerol phosphate, forming triglycerides.
            ▪ These resulting triglycerides are stored in droplets until needed.
            ▪ Norepinephrine from nerve endings stimulates the cAMP system,
                which activates hormone-sensitive lipase.
            ▪ Hormone-sensitive lipase hydrolyses stored triglycerides to free fatty
                acids and glycerol.
            ▪ These substances diffuse into the capillary, where free fatty acids are
                bound to the hydrophobic moiety of albumin for transport to distant
                sites for use as an energy source
     o Thermogenin dissipates the proton electrochemical gradient ? BROWN
            ▪ We have a specific protein – thermogenin.
            ▪ We have the transport of protons and electrons from the trycarboxilic
                acid cycle
            ▪ The protons are pumped into the intermembranous space →
                Electrochemical gradient
            ▪ The protons then go down the gradient (A FAVOR DO)The energy of
                electrochemical gradient from the thermogenin protein are converted
                into heat
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             ❖ Cartilage
                  o Tissue characterized by chondrocytes and an ECM enriched with GAGs and
                      proteoglycans
                  o Variations in the ECM composition originate hyaline, elastic and fibrous
                      cartilages.
                  o Hyaline Cartilage: In embryo serves as a temporary skeleton. In adults is
                      located in the articular surfaces of movable joints, in the walls of the larger
                      respiratory passages (nose, larynx, trachea, bronchi), in the ventral ends of ribs
                      and at the ends of bones (epiphyseal plate)
                  o Chondrocyte are located in matrix lacunae (type of ECM (purple thing
                      surrounding the purple thing (cell itself)))
                  o Perichondrium:
             ❖ Bone
                  o Tissue supports fleshly structures, protects vital organs and harbours the
                      bone marrow where blood is formed.
                  o Highly vascularized and metabolically active
                  o Serve also as reservoir of ions (Calcium, Phosphate)
                  o ECM is mineralized ECM and inside lacunae, osteocytes/osteoblasts which
                      synthesize the organic ECM, and osteoclasts which make reabsorption and
                      remodelling of the bone tissue.
                  o The lacunae and canaliculi filled with air deflect the light and appear dark,
                      showing the communication between these structures through which
                      nutrients derived from blood vessels flow.
Bone reabsorption
   1. Lysosomal enzymes packaged in Golgi complex and protons are released into the bone matrix
   2. The acidification facilitates the dissolution of calcium phosphate from bone and is the optimal pH
      for the activity of lysosomal hydrolases (e.g. collagenases).
   3. Bone matrix is thus removed and the products of bone resorption are taken up by the osteoclast’s
      cytoplasm, probably digested further and transferred to blood capillaries
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o Blood consists of cells (erythrocytes, platelets and leukocytes) and plasma
  (ECM): albumins, -globulins, lipoproteins, prothrombinand fibrinogen,
  signaling molecules, waterand ions. (serumis plasma without the coagulated
  proteins)
o Main components and functions of blood
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                     o CO2 and O2 transport by erythrocytes and plasma
Blood Clotting
   1. An injury to the lining of a blood vessel exposes collagen fibers; Platelets adhere and become
      sticky
   2. Platelets release substances that cause the vessel to contract. Sticky platelets form a plug and
      initiate the formation of a fibrin clot.
   3. The fibrin clot seals the wound until de vessel wall heals.
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                     o Bone marrow (myeloid tissue): is found in the hollow interior of bones. It
                       constitutes 4% of total body weight, and is responsible for hematopoiesis
                       (erythropoiesis, granulonopoiesis, monocytopoiesis, megacaryocytopoiesis
                       or thrombopoiesis)
                           ▪ It is the place for B lymphocytes maturation
                           ▪ Network of stromal cells and hematopoietic cells (fibroblasts,
                              macrophages, adipocytes, osteoblasts, osteoclasts, endothelial cells
                              forming the sinusoids)
                           ▪ Removes (like liver and spleen) damaged erythrocytes
              ❖ Lymphoid Tusse:
                   o Circulating lymphocytes originate (lymphopoiesis) mainly in the thymus and
                     the peripheral lymphoid organs (spleen, lymph nodes, tonsils)
                   o Some migrate to thymus where they become T/lymphocytes and other
                     differentiate at bone marrow, B-lymphocytes.
                   o The lymphoid organs and lymphatic vessels are widely distributed in the body.
                   o The lymphatic vessels collect lymph from most parts of the body and deliver it
                     to the blood circulation primarily through the thoracic duct.
Muscle Tissue
   •   Muscle Tissue is divided in 3 types:
         o Cardiac muscle
                 ▪ It is composed of irregular branched cells bound together longitudinally by
                    intercalated disks
                 ▪ Contracts vigorously, rhythmically and under involuntary control (at the same
                    time)
                 ▪ Has almost no regenerative capacity beyond early childhood
                 ▪ Note the cross striation and the intercalated disks (arrowheads) which are
                    enriched in gap junctions to assure ionic continuity between adjacent cells. Thus,
                    muscle to act as a syncytium allowing the signal to contract to pass in a wave from
                    cell to cell.
                 ▪ Contraction: similar to skeletal muscle
         o Smooth muscle
                 ▪ It is an agglomerate of fusiform cells
                 ▪ Contracts slowly and under involuntary control
                 ▪ Contraction does not rely in a paracrystalline organization of actin and myosin and
                    depends on the phosphorylation of myosin and of calcium binding protein,
                    calmodulin, but not dependent of tropomyosin
                 ▪ SM is capable of active regeneration
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 Muscle Contraction (SM)
    1. Intracellular Ca2+ concentration increases when Ca2+ enters cell and is released from
       sarcoplasmatic reticulum
    2. Ca2+ binds to calmodulin (CaM)
    3. Ca2+-Calmodulin activates myosin light chain kinases (MLCK)
    4. MLCK phosphorylates light chains in myosin heads and increases myosin ATPase activity
    5. Active myosin crossbridges slide along actin and create muscle tension
          o Skeletal muscle
               ▪ It is composed of large, elongated, multinucleated fibers
               ▪ Contracts quickly, forcefully and under voluntary control
               ▪ Long multinucleated fibers, form bundles and result from
                   the fusion of embryonic mononucleated myoblasts
               ▪ Can undergo limited regeneration (from inactive
                   myoblasts)
               ▪ Sarcomeres are the units of contractions
                       • Thick ones: myosin
                       • Thin ones: actin
                 ❖ Sequential activation of gated ion channels at a neuromuscular junction (or motor
                   end-plate)
                    1. Arrival of action potential at the terminus of a presynaptic motor neuron
                       induces opening of voltage-gated Ca2+ channels and
                    2. subsequently release of acetylcholine, which triggers opening of the ligand-
                       gates nicotinic receptors in the muscle plasma membrane
                    3. The resulting influx of Na+ produces a localized depolarization of the
                       membrane, leading to opening of voltage-gated Na+ channels and generation
                       of an action potential
                    4. When the spreading depolarization reaches T tubules, it triggers opening of
                       voltage-gated Ca2+ channels and release of Ca2+ from the sarcoplasmatic
                       reticulum into the cytosol
                    5. The rise in cytosolic Ca2+ causes muscle contraction
Muscle Contraction (Skeletal Muscle)
   1. Initiated by binding of Ca2+ to the TnC unit of troponin, which exposes the myosin binding site
      on actin (cross-hatched area).
   2. The myosin head binds to actin and the ATP is hydrolysed yielding energy, which produces a
      movement of the myosin head.
   3. As
Nervous    a consequence of this change in myosin, the bound thin filaments slide over the thick
        Tissue
      filaments reducing the distance between the Z-lines, thereby shortening of the whole muscle
      fiber                                                                                          9
  •   It is composed of nerve cells (neurons) which sense, process and respond to features of both
      internal and external environment, glial cells (neuroglia) which occupy space between neurons
      and modulate their functions
  •   Each neuron has many interconnections with other neurons
  •   Neurons are responsible for reception, transmission and processing of stimuli, the triggering of
      certain cell activities and release of neutransmitters. Generally, receive information via their
      dendrites and transmit information via their axons to the other neurons or other cells forming
      synapses.
  •   Glial Cells: Physically support neurons and perform many housekeeping functions
  •   All these cells are derived from progenitor cells in neural tube expect microglia which is formed
      at bone marrow.
Membrane Potential
  •   Neurons have an electric charge difference across their membranes. The difference in voltage
      across membrane is called membrane potential. In an unstimulated neuron is called resting
      potential. Nerve impulses are also called action potentials and travel along the plasma
      membrane.
  1. The negative resting potential is created by the 3Na+/2K+ ATPase and K+ and Na+ ion
     channels.
  2. Na+-K+ pump moves 2K+ ions inside the cells as 3Na+ ions are pumped out.
  3. K+ ions diffuse out of the cell at a faster rate than Na+ ions diffuse into the cells because
     neurons have more K+ leakage channels than Na+ leakage channels.                                10
•   Action potentials result from rapid changes in voltage-gated Na+ and K+ channels.
•   An action potential is a rapid reversal in charge across a portion of the plasma membrane
    resulting from the sequential opening and closing of voltage-gated sodium and potassium
    channels. These changes in voltage-gated channels occur when the plasma membrane
    depolarizes to a threshold level.
•   Synapses are functional connections for communication between neurons or neurons and
    cells.
•   Synaptic transmission begins with the arrival of an action potential
•   Synapses can be excitatory or inhibitory (the neuromuscular is always excitatory
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Molecular mechanism of vesicle fusion
   •   SNAREs can be divided into 2 categories:
         o Vesicle or v-SNAREs: which are incorporated into the membranes of transport vesicles
            during budding
         o Target or t-SNAREs: which are associates with nerve terminal membranes
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